Our long-term goal of this exploratory research proposal is to determine how chromosome conformation and subnuclear position affect the host response to viruses. Significance and role of large-scale nuclear processes of folding and juxtaposition of chromosomal fibers during innate immune response to viruses remain relatively unknown. However, these processes represent unexplored epigenetic targets for modulating the innate immune system for potential therapies. To understand these nuclear processes involved in anti-viral response in human cells, we will characterize the molecular mechanisms that modulate chromosomal conformation and subnuclear location of the type I interferon locus in the genome of diploid fibroblasts and lymphoblasts during viral infection. A better understanding of the regulatory mechanisms involved in the production of type I interferons is fundamental to the development of therapeutic strategies for treating viral infections and inflammatory diseases such as autoimmunity.